Disease relevance of RSS

• The chemical mechanism of hairpin opening by RAGs resembles RSS cleavage and 3' end processing by HIV integrase and Mu transposase in that these reactions can proceed through alcoholysis [1].
• Owing to its location in 7p11.2-p12, GRB10 has been considered a candidate gene for the imprinted growth disorder, the Silver-Russell syndrome (SRS), but its predominantly biallelic expression argues against involvement in the syndrome [2].
• We report a proximal 7p interstitial inverted duplication in a mother and daughter both of whom have features of SRS, including marked short stature, low birth weight, facial asymmetry and 5th finger clinodactyly [3].
• We report a case of IUGR in a newborn with SRS stigmata [4].
• Examples of classic human disorders related to genomic imprinting are Beckwith-Wiedemann syndrome (chromosome 11), Prader-Willi/Angelman syndromes (chromosome 15), Russell-Silver syndrome (chromosome 7), and Albright hereditary osteodystrophy (chromosome 20) [5].
• Among RSS patients, prominent forehead, relative macrocephaly, body asymmetry, and low BMI were significantly associated with ICR1 LOM [6].

Psychiatry related information on RSS

• However, 8q12 still remains as one potential locus for a gene whose mutations may cause the clinical findings of SRS and which could be included in a larger deletion in a proband who has additional mild mental retardation [7].
• We examined the psychometric properties of the Self-Regulation Scale (SRS; Schwarzer, Diehl, & Schmitz, 1999), a measure of attention control in goal pursuit, in 2 independent studies [8].
• We found support for the criterion validity of the SRS in terms of positive correlations with measures of general and domain-specific self-efficacy, proactive coping, and positive affect and in terms of negative correlations with depressive symptoms and negative affect [8].

High impact information on RSS

• Mutations in either RAG1 or RAG2 that interfere with RSS cleavage also interfere with hairpin opening, suggesting that RAGs have a single active site that catalyzes several distinct DNA cleavage reactions [1].
• We characterize 13 patients with DVD--5 with hemizygous paternal deletions spanning the FOXP2 gene, 1 with a translocation interrupting FOXP2, and the remaining 7 with maternal uniparental disomy of chromosome 7 (UPD7), who were also given a diagnosis of Silver-Russell Syndrome (SRS) [9].
• Hypomethylation of the H19 gene causes not only Silver-Russell syndrome (SRS) but also isolated asymmetry or an SRS-like phenotype [10].
• To date, three imprinted genes-PEG1/MEST, gamma2-COP, and GRB10-have been identified on chromosome 7, but their role in the etiology of SRS remains uncertain [11].
• Intermediates in V(D)J recombination: a stable RAG1/2 complex sequesters cleaved RSS ends [12].

Chemical compound and disease context of RSS

• While emphasizing the need for a high index of diagnostic suspicion for congenital malformations and syndromic causes of IUGR in the African sub-region, we suspect a possible etiologic association of haloperidol embryopathy with RSS in the current case [13].
• Their source was: (1) carious material from advanced root lesions (ARL), (2) plaque from sound root surfaces of root-caries-free subjects (SRS), (3) plaque from "white spot" coronal lesions and sound coronal surfaces of caries-active subjects, and (4) plaque from sound coronal surfaces of caries-free subjects [14].
• Human slow-reacting substance of anaphylaxis (SRS-A) and calcium ionophore-induced human SRS released prostaglandin-like substances and rabbit aorta contracting substance (RCS) from guinea-pig lungs [15].
• The objective of this study was to evaluate the efficacy of Norian skeletal repair system (SRS), a novel biodegradable and injectable form of calcium phosphate cement with a composition similar to that of cancellous bone, as a carrier for moxifloxacin, which is the most potent quinolone agent against staphylococci and Enterobacteriaceae [16].

Biological context of RSS

• Imprinted gene(s) on human chromosome 7 are thought to be involved in Russell-Silver syndrome (RSS), based on the fact that approximately 10% of patients have maternal uniparental disomy of chromosome 7 [17].
• Documentation of maternal uniparental disomy of chromosome 7 in 10% of patients with Russell-Silver syndrome (RSS), characterized by prenatal and postnatal growth retardation and dysmorphic features, has suggested the presence of an imprinted gene on chromosome 7 whose mutation is responsible for the RSS phenotype [18].
• The fact that monoallelic GRB10 expression was observed from the maternal allele in this study suggests but does not prove that these maternally transmitted mutant alleles contribute to the RSS phenotype [18].
• Antigen receptor gene rearrangements are initiated by the RAG1/2 protein complex, which recognizes specific DNA sequences termed RSS (recombination signal sequences) [19].
• In a systematic screening with microsatellite markers, for matUPD7 cases among patients with SRS, we identified a patient who had a small segment of matUPD7 and biparental inheritance of the remainder of chromosome 7 [11].

Anatomical context of RSS

• Recent experiments using artificial recombination substrates in cultured cells have shown that efficient cleavage requires a pair of RSS, one with a 12 nucleotide spacer and one with a 23 nucleotide spacer [20].
• In the lymphocytes of SRS patients, no aberrant expression patterns of two splice variants (alpha and beta) of PEG1/MEST were detected when they were compared with normal samples [21].
• CONCLUSIONS: We conclude that the rapid growth acceleration to GH treatment does not alter the lower limb asymmetry in children with RSS [22].
• Placental anomalies (velamentous cord insertion, single umbilical artery, placental hypotrophy) for the small-for-date twins and a twin-twin transfusion syndrome confirmed at 21 weeks of amenorrhea suggest that early hemodynamic disorders may reveal or trigger RSS which has been considered to be of genetic origin [23].
• CASE: The diagnosis of RSS in the proband was suspected prenatally because trisomy 7 mosaicism (47,XX,+7[13]/46,XX[19]) and maternal uniparental heterodisomy 7 were both found in amniotic fluid cells [24].

Associations of RSS with chemical compounds

• STUDY DESIGN: Twenty-four children with RSS under the age of 4 years, who had either clinical symptoms of hypoglycaemia or previous evidence of biochemically documented hypoglycaemia, were admitted to hospital for 48 hours to perform a 24-h cortisol/glucose profile and a diagnostic fast in those who did not develop spontaneous hypoglycaemia [25].
• Since the initial report by Silver et al (1953), more than 50 examples of the Russell-Silver syndrome have been reported [26].
• Although the last-named drugs inhibit other arachidonate metabolic pathways too, conclusive evidence that the metabolites of the lipoxygenase pathway, and leukotrienes in particular, mediate the LAI response was the fact that FPL 55712, a competitive antagonist of SRS, nullified a positive response at levels as low as 10(-13) M [27].
• No mutations were found in the cysteine-rich region involved in ligand binding (exon 3) or the ATP binding region (exon 16) which could contribute to the SRS phenotype [28].
• Thus SRS joins histamine and ECF-A as a preformed mediator [29].

Regulatory relationships of RSS

• PEG1/MEST is an imprinted gene on chromosome 7q32 that is expressed only from the paternal allele and is a candidate gene for SRS [21].

Other interactions of RSS

• Imprinting of human GRB10 and its mutations in two patients with Russell-Silver syndrome [18].
• However, analysis of ten SRS patients revealed no mutations in CPA4 [30].
• The hypothesis that sub-microscopic duplications including GRB10 and IGFBP1 is a cause of SRS remains a possibility and warrants further investigation [3].
• Many imprinted genes contribute to growth, either as growth factors, such as insulin-like growth factors (IGF2 in Beckwith-Wiedemann syndrome), or as growth inhibitors, such as the GRB10 gene in Russell-Silver syndrome [5].
• Russell-Silver syndrome: molecular diagnosis of maternal uniparental disomy of chromosome 7 using methylation-specific polymerase chain reaction assay and single nucleotide polymorphisms genotyping [31].

Analytical, diagnostic and therapeutic context of RSS

• The characteristic features, differential diagnoses, etiologic postulates/current cytogenetic and molecular genetic findings of RSS are fully reviewed in the discussion [13].
• Russell-Silver syndrome (RSS) is a disorder characterized by pre- and post-natal growth deficiency, triangular facies, relative macrocephaly, and body asymmetry [32].
• PURPOSE: The objective of this work was to measure whole body radiation doses in a humanoid phantom from linear accelerator-based cranial stereotactic radiosurgery/therapy (SRS/T), using different beam arrangements [33].
• Thirty-three SRS probands, with normal karyotypes, and their parents were investigated for the presence of both copies of IGFIR by gene dosage analysis of Southern blot hybridisation [28].
• PURPOSE: To prospectively evaluate efficacy and side effects of hypofractionated stereotactic radiotherapy (hfSRT) for irresectable brain metastases not amenable to radiosurgery (SRS) [34].

References